Recent studies have furnished much new information about the fundamental principles of defibrillation. From this new information, we have formed several hypotheses which together may explain how shocks defibrillate. The goal of this grant is to use new investigational tools to test these hypotheses in animals. One new tool, a 528-channel mapping system to record before, during, and after defibrillation shocks will be used to test these hypotheses: (1) Following shocks slightly weaker than needed to defibrillate, the first few postshock activation fronts arise by reentry from regions exposed to a low shock potential gradient. (2) Defibrillation fails because these postshock activation fronts form new reentrant pathways outside the low potential gradient region. (3) These new reentrant pathways frequently form in the high potential gradient region adjacent to defibrillation electrodes. (4) Biphasic are superior to monophasic waveforms for defibrillation because they are less likely to give rise to postshock activation fronts in the low gradient region and/or because the postshock activation fronts are less likely for form new reentrant circuits in the high gradient region. (5) Very high voltage defibrillation shocks can fail because postshock activation arises from the high gradient region. (6) Following myocardial infarction, reentrant pathways also form in the peri-infarction region. We will use another investigational tool, the double barreled electrode in a tissue bath, to understand the relationship between the extracellular potential gradient and the change it causes in the transmembrane potential as well as to investigate the effects of this transmembrane potential change on the ensuing action potentials. These studies will test the following hypotheses: (1) The change in transmembrane potential caused by a shock is linearly proportional to the shock potential gradient up to a 'breakdown' transmembrane potential more than 400 mV. (2) The ability of a shock waveform to stimulate a new action potential, cause action potential prolongation, and defibrillate is directly related to the peak change it causes in the transmembrane potential. (3) The monophasic waveform that defibrillates with the lowest energy causes the greatest change in transmembrane potential for a given energy. (4) The biphasic waveform that defibrillates with the lowest energy achieves the greatest change in transmembrane potential for a given energy during the 1st phase and quickly restores the transmembrane potential to a lower, more physiologic, value during the 2nd phase. (5) The change is transmembrane potential over space during a shock exhibits a 'sawtooth' pattern with each sawtooth corresponding to a single cell or group of cells. Testing these hypotheses will greatly increase our understanding of the basic mechanisms of defibrillation. By pinpointing the factors responsible for defibrillation, these studies would suggest how defibrillation can be improved to increase the likelihood of success.